Consolidation Therapy With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 in Patients With Chronic Lymphocytic Leukemia Following Upfront Chemotherapy With Pentostatin, Cyclophosphamide and Rituximab
The purpose of this Phase I study is to test the safety and effect of specially prepared cells collected from the patients called "modified T cells." We want to find a safe dose of modified T cells for patients who have disease remaining after initial chemotherapy. We also want to find out what effects these T cells have on you and your leukemia.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Consolidation Therapy With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 in Patients With Chronic Lymphocytic Leukemia Following Upfront Chemotherapy With Pentostatin, Cyclophosphamide and Rituximab|
- toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Criteria for toxicity: Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
- maximum tolerated dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]If none of the initial 3 patients in a cohort experience a dose limiting toxicity (DLT) then the next dose level will be studied in another cohort of 3 patients
- disease response [ Time Frame: 2 years ] [ Designated as safety issue: No ]The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. Radiographic studies are not required but those that were abnormal pre-treatment will be repeated to document the degree of maximal response.
- change in cellular and cytokine tumor microenvironment [ Time Frame: 2 years ] [ Designated as safety issue: No ]Cellular tumor microenvironment analysis: The presence of regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs), as well as the presence of immune effector cells including dendritic cells, NK cells, and effector T cells will be assessed by fluorescence-activated cell sorting (FACS).
- the impact of infused modified T cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]Persistence of gene-modified T cells is defined by the presence of any percentage of detectable cells. The percentage of gene-modified T cells/ total T cells will be recorded for all patients treated at each dose level. In addition, gene-modified T cells will be measured daily for two days, weekly for eight weeks and monthly for six months (by FACS and RT-PCR).
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||August 2014|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: consolidative therapy with autologous T cells genetically
A phase I trial of consolidation therapy with autologous T cells genetically targeted to the B cell specific antigen CD19 for patients with chronic lymphocytic leukemia following upfront chemotherapy with pentostatin, cyclophosphamide and rituximab.
Patients will first receive a single infusion of therapy conditioning with cyclophosphamide.Biological: modified T cells
followed by consolidative therapy with the modified T cells in 3 planned cohorts.
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Jae Park, MD||Memorial Sloan-Kettering Cancer Center|